The invention pertains to catheters and catheter balloons that include drug coatings for delivery to a site within a body passageway.
Sometimes following an initially successful angioplasty or other primary treatment restenosis occurs within weeks or months of the primary procedure. Restenosis results at least in part from smooth muscle cell proliferation in response to the injury caused by the primary treatment. This cell proliferation is referred to as “hyperplasia.” Blood vessels in which significant restenosis occurs will typically require further treatment.
A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Previously proposed strategies include prolonged balloon inflation, treatment of the blood vessel with a heated balloon, treatment of the blood vessel with radiation, the administration of anti-thrombotic drugs following the primary treatment, stenting of the region following the primary treatment, the use of drug-eluting stents, use of drug delivery balloons, cutting balloons, cryotherapy systems and the like.
Drug delivery balloons that deliver drug to an internal site upon expansion are known. Some involve perfusion of a drug composition through the balloon wall or from a spongy layer on the balloon wall. Others involve delivery of solid particulate drug, often carried in a polymer or other excipient to the site.
Delivery of drug from the surface during expansion provides benefits of pushing the drug into the specific tissue to be effected and is especially suited for delivering drugs that prevent restenosis during a dilation of a stenotic lesion.
Known drug delivery balloons include paclitaxel coated balloons. In some cases paclitaxel has been applied directly to the balloon or to a coating placed on the balloon. In other cases paclitaxel has been formulated with an excipient that may be polymer, a contrast agent, a surface active agent, or other small molecules that facilitate adhesion to the balloon and/or release from the balloon upon expansion. The formulations have typically been applied from solution, and may be applied to the entire balloon or to a folded balloon, either by spraying, immersion or by pipette along the fold lines or onto a folded or unfolded balloon.
Earlier investigations of paclitaxel coated balloons have shown that it is desirable to control the morphology of the drug on the balloon, that with paclitaxel coated balloons paclitaxel dihydrate paclitaxel crystalline form facilitates longer tissue residence time, that the formation of crystalline paclitaxel dihydrate can be controlled by use of vapor annealing of the balloon, and that temperature change at the delivery site can be used to trigger a change in the bonding properties of a drug or drug-containing composition to the balloon.
A variety of techniques have been described for preparing drug coated balloons.
Several balloon coating techniques previously described involve coating a folded and wrapped balloon, by immersion, spraying, pipette, syringe or use of applicator tip such as a wire or capillary that contacts a balloon. In some techniques wicking into the folds is achieved in varying degrees and sometimes residual coating on the outer surface is wiped out. In one technique an applicator is inserted under the fold edge to inject coating solution into the folds. Within the folds the drug coating texture and thickness varies depending on whether the fold is completely filled, and the varied spacing between outer surfaces of the balloon. The result is a coating that is non-uniform and which varies in delivery behavior between its thickest and thinnest portions. If an inflated balloon is coated a more uniform coating is provided. However the balloon must subsequently be folded and wrapped. Folding machinery typically application of heated prongs as the balloon is evacuated or drawing the balloon through a die opening as pressure is withdrawn. Drug coatings for DEB balloons are not practically put through conventional folding machinery. They leave material on the contacting parts of folding machines which interferes with the operation and which also causes reduction of the coat weight uniformity.
There is an ongoing need for improved methods for forming drug delivery balloon catheters that provide durable coatings which can be reliably manufactured.